Stress and hippocampal volume in rodents, a longitudinal study

压力对记忆的影响至少部分是由于它对海马体的影响，海马体是一个对学习和记忆很重要的大脑区域。虽然慢性应激可以减少海马体积，但海马萎缩的功能意义尚不清楚。理解海马萎缩的功能意义的困难可能部分是由于几乎完全使用横断面方法来研究应激和非应激个体之间的海马体积差异。然而，横断面研究未能揭示因果关系。另一个问题是，在大多数压力研究中，未能控制压力敏感性的个体差异。对经历过大规模创伤事件的人进行的精神病理学调查显示，并非所有人都受到这些事件的影响，因此有些人对创伤具有弹性。** 这个新的NSERC应用程序是建立在我的实验室的一个新兴的长期目标，以揭示应激诱导海马萎缩的功能意义和机制。使用非侵入性MRI方法测量应激暴露前后的海马体积，我们发现易受慢性社会失败应激影响的小鼠显示应激诱导的体积变化。尽管如此，这些变化并没有在对长期社会失败有弹性的小鼠中发现。我们的短期目标是使用这种社会失败模型，该模型允许我们分离对慢性应激敏感或有弹性的小鼠，以测试以下假设：1）有弹性的小鼠表现出对应激诱导的海马萎缩的抵抗力; 2）慢性应激对背侧海马和腹侧海马的体积产生相反的影响，背侧海马和腹侧海马分别负责空间记忆和情绪记忆的形成，3）应激诱导的海马萎缩与树突重组和小胶质细胞增殖有关。这项研究的发现不仅可以促进我们对应激诱导海马萎缩的功能意义和机制的理解，而且还可以为纵向研究小鼠脑结构的变化开辟新的研究途径。这项研究计划补充了我的实验室正在进行的研究，以调查应激对海马突触功能的影响。这项研究计划的培训可以使受训者能够在小鼠身上使用非侵入性成像方法，这些方法是强大但新兴的研究技术，可以帮助他们在学术界和工业界发展自己的职业生涯。

The impact of stress on memory is at least partly due to its influences on the hippocampus, a brain region that is important for learning and memory. Although chronic stress could reduce hippocampal volume, the functional significance of hippocampal shrinkage remains unclear. The difficulty of understanding the functional significance of hippocampal shrinkage may be partly caused by the almost exclusive use of a cross-sectional approach to investigate hippocampal volume differences between stressed and non-stressed individuals. Cross-sectional studies however fail to reveal causality. Another problem is related to the failure to control for individual differences in stress susceptibility in most stress studies. Investigating psychopathologies in people that had experienced wide scale traumatic events revealed that not all people are similarly affected by these events, so that some individual were resilient to trauma. ******This new NSERC application is built on an emerging long term objective of my laboratory to reveal the functional significances and mechanisms of stress-induced hippocampal shrinkage. Using a non-invasive MRI approach to measure hippocampal volume before and after stress exposure, we have found that mice that are susceptible to chronic social defeat stress displayed stress-induced volume changes. Nonetheless, these changes were not found in mice that are resilient to chronic social defeat. Our short term objective is to use this social defeat model that allows us to separate mice that are susceptible or resilient to chronic stress to test the following hypotheses: 1) resilient mice exhibit a resistance to stress-induced hippocampal shrinkage; 2) chronic stress exerts opposing effects on the volume of the dorsal and ventral hippocampus, which are responsible for spatial and emotional memory formation, respectively, and 3) stress-induced hippocampal shrinkage is related to dendritic reorganization and microglia proliferation.******Findings from this research program could not only advance our understanding of the functional significance and mechanisms of stress-induced hippocampal shrinkage, but also allow us to develop a new research avenue for longitudinally investigating changes in mouse brain structures. This research program complements the ongoing research of my lab to investigate the impact of stress on hippocampal synaptic function. Training from this research program could equip trainees to use non-invasive imaging approaches on mice, which are powerful but newly emerging research techniques that could help them develop their career in both academia and industry.